Endothelin (ET)-1, a potent endothelium-derived vasoconstrictor peptide, has several properties suggestive of its potential pathophysiological role in pulmonary hypertension. Bosentan is an endothelial receptor antagonist and efficacious in treating pulmonary hypertension. The objectives of this study were to evaluate the effect of bosentan on monocrotaline (MCT)-induced pulmonary hypertension in rats and to correlate it with the gene expression of ET-1 and ET A receptors.
Sprague-Dawley rats were divided into three groups: control group, MCT group (60 mg/kg), bosentan group (MCT 60 mg/kg plus 6.25 mg/day bosentan orally). The mean body weights of the rats in the MCT and bosentan groups were significantly lower than the control group on day 7, 14, and 28. Administration of bosentan significantly inhibited the progression of right ventricular hypertrophy on day 28. Quantitative analysis of peripheral pulmonary arteries revealed that the increase in medial wall thickness after MCT injection was significantly attenuated in the bosentan group on day 28. In addition, an increase in the number of intra-acinar muscular arteries after MCT injection was reduced by bosentan on day 14. The expressions of ET-1(4.19±1.84 vs 1±0.20) and ET receptor A (3.35±1.26 vs 1±0.34) gene were significantly increased in MCT group on day 5. Serum ET-1 concentrations in the MCT group were higher than the control group on day 28.
In conclusion, ET-1 expression correlates with the progression of cardiopulmonary alterations in rats with MCT-induced pulmonary hypertension. Administration of bosentan inhibited pulmonary vascular hypertrophy and right ventricular hypertrophy during development of MCT-induced pulmonary hypertension in rats.